Parashar Arun, Jha Dhruv, Mehta Vineet, Chauhan Bonney, Ghosh Pappu, Deb Prashanta Kumar, Jaiswal Mohit, Prajapati Santosh Kumar
School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan 173 212, India.
Birla Institute of Technology, India.
Ageing Res Rev. 2024 Apr;96:102271. doi: 10.1016/j.arr.2024.102271. Epub 2024 Mar 16.
Alzheimer's disease (AD) is caused by the aging process and manifested by cognitive deficits and progressive memory loss. During aging, several conditions, including hypertension, diabetes, and cholesterol, have been identified as potential causes of AD by affecting Sonic hedgehog (Shh) signalling. In addition to being essential for cell differentiation and proliferation, Shh signalling is involved in tissue repair and the prevention of neurodegeneration. Neurogenesis is dependent on Shh signalling; inhibition of this pathway results in neurodegeneration. Several protein-protein interactions that are involved in Shh signalling are implicated in the pathophysiology of AD like overexpression of the protein nexin-1 inhibits the Shh pathway in AD. A protein called Growth Arrest Specific-1 works with another protein called cysteine dioxygenase (CDO) to boost Shh signalling. CDO is involved in the development of the central nervous system (CNS). Shh signalling strengthened the blood brain barrier and therefore prevent the entry of amyloid beta and other toxins to the brain from periphery. Further, several traditional remedies used for AD and dementia, including Epigallocatechin gallate, yokukansan, Lycium barbarum polysaccharides, salvianolic acid, and baicalin, are known to stimulate the Shh pathway. In this review, we elaborated that the Shh signalling exerts a substantial influence on the pathogenesis of AD. In this article, we have tried to explore the various possible connections between the Shh signalling and various known pathologies of AD.
阿尔茨海默病（AD）由衰老过程引起，表现为认知缺陷和进行性记忆丧失。在衰老过程中，包括高血压、糖尿病和胆固醇在内的几种情况已被确定为通过影响音猬因子（Shh）信号传导而成为AD的潜在病因。除了对细胞分化和增殖至关重要外，Shh信号传导还参与组织修复和预防神经退行性变。神经发生依赖于Shh信号传导；该信号通路的抑制会导致神经退行性变。参与Shh信号传导的几种蛋白质-蛋白质相互作用与AD的病理生理学有关，例如蛋白连接蛋白-1的过表达会抑制AD中的Shh信号通路。一种名为生长停滞特异性蛋白1的蛋白质与另一种名为半胱氨酸双加氧酶（CDO）的蛋白质共同作用以增强Shh信号传导。CDO参与中枢神经系统（CNS）的发育。Shh信号传导强化了血脑屏障，因此可防止淀粉样β蛋白和其他毒素从外周进入大脑。此外，几种用于治疗AD和痴呆的传统药物，包括表没食子儿茶素没食子酸酯、 yokukansan、枸杞多糖、丹酚酸和黄芩苷，已知可刺激Shh信号通路。在本综述中，我们阐述了Shh信号传导对AD的发病机制有重大影响。在本文中，我们试图探索Shh信号传导与AD的各种已知病理之间的各种可能联系。
